This invention relates to a method to reduce stress induced suppression of the immune system of an animal. The method comprises administering to an animal, prior to, during and/or subsequent to the stress event, a nutritional product comprising a structured glyceride component and an antioxidant system. The invention also relates to a nutritional product that comprises an antioxidant system and a structured glyceride component.
Stress is a physical, chemical or emotional factor that causes bodily or mental tension and may be a factor in disease causation. The notion that excessive stress can. alter host defenses and increase susceptibility to illness is not new. A publication by Pedersen, et al., provides a review of work conducted in the area of stress and disease. See Pedersen, et al., xe2x80x9cThe immune system during exposure to extreme physiological conditionsxe2x80x9d, Inter J. Sports Med. 1994 15:5116-5121.
In recent years, rapid advances in the field of immunology have generated intense interest in the interaction between stress induced by psychosocial, nutritional and physical factors and the immune system. A major premise of this work is that stress may enhance vulnerability to disease by exerting an immunosuppressive effect. This may especially be true of diseases intimately connected with immunologic mechanisms such as infection, malignancy and autoimmune disease.
Studies demonstrating immune alterations in human stress encompass a number of models wherein most types of experimental and naturally occurring stresses have been associated with alteration of the components of the immune system. Some of the earliest work was done by the United States National Aeronautic Space Administration (NASA). The NASA studies showed that white blood cells and T-lymphocytes were elevated during the splash-down phase of space flight. However, there was impairment in the lymphoproliferative response to mitogenic stimulation during the first three (3) days after return to earth. A slight decrease in the stimulation response of lymphocytes was also observed prior to launch, possibly due to anticipation. A good overview of stress and immune function can be found in xe2x80x9cStress, Immunity and Illnessxe2x80x94A Reviewxe2x80x9d, authored by Dorian and Garfinkel, Psychological Medicine, 17:393-407 (1987).
Physical activity and exercise are also known to produce a variety of alterations to the immune system. The effects of vigorous exercise appear to depress immune function and may compromise host defenses against upper respiratory tract infections. Epidemiological studies have generally shown a greater risk of upper respiratory tract infections with vigorous levels of exercise. See Heath, et al., xe2x80x9cExercise and Upper Respiratory Tract Infectionsxe2x80x9d, Sports Medicine, 14(6) 353-365 (1992).
As humans age, they experience a decline in most cell mediated and humoral immune responses. The elderly are often stressed from various infections, bereavement, cancer and nutritional deficiencies. The elderly are also often stressed from environmental factors such as inadequate housing and mental deficiencies. Supplementation with modest physiological amounts of micronutrients has been shown to decrease nutritional deficiencies and improve various measures of immunity and decrease the frequency of infection-related illnesses in ninety six (96) elderly subjects (mean age 75). See Chandra R. K., xe2x80x9cEffect of Nutrients and Trace Element Supplementation on Immune Responses and Infection in Elderly Subjects;xe2x80x9d Lancet 1992, Vol. 340, pp. 1124-1127. The factors of age, exercise, malnutrition and stress have also been investigated by Hoffman-Goetz, L., et al., xe2x80x9cExercise and Immune Functionxe2x80x9d, CRC Press, Boca Raton (1996).
Infection is characterized by a loss of Ussue lipid, protein and micronutrients. This is partially the result of the cytokine mediated response designed to, support the activities of the immune system and to protect the host. Grimble in xe2x80x9cMalnutrition and the Immune Responsexe2x80x9d, Transactions of the Royal Society of Tropical Medicine and Hygiene (1994) 88, 615-619, reports the influence of protein and amino acid intake on cytokine biology. The author also discusses the modulation of cytokine biology by fat and micronutrient intake.
Blood leukocytes represent only a small portion of the total number of leukocytes in the body, yet they provide an important representation of the state of activation of the immune system. It is known that acute stress induces large, rapid, and reversible changes in the distribution of peripheral blood leukocyte subpopulations. Leukocytes and other subpopulations of lymphocytes were examined by the inventors of this patent application to determine if nutritional supplementation could alter the response of the immune system to stress. The data reported below support the conclusion that the inventive composition is useful in preventing or reducing stress induced suppression of the immune system.
Convincing evidence has been accumulated to show that certain nutrients, particularly vitamins C and E, xcex2-Carotene and calcium, are useful in the prevention and management of coronary heart disease, hypertension, certain cancers and osteoporosis. In addition, vitamins C, E and xcex2-Carotene (antioxidant nutrients) seem to offer protection against exercise mediated free radical damage. Thus, it has been suggested that an antioxidant nutrient regimen should be made an integral part of any exercise program directed towards prevention/management of chronic disease and promotion of health. An excellent discussion of antioxidants and physical performance can be found in: (1) xe2x80x9cAntioxidants in Infectionxe2x80x9d by Keuchs, J. Nutr. Sci. Vitaminol., S23-S33 (1993); (2) Aruoma, xe2x80x9cFree Radicals and Antioxidant Strategies in Sportsxe2x80x9d, J. Nutr. Biochem., 1994, vol. 5, pp. 370-380; and (3) Clarkson, xe2x80x9cAntioxidants and Physical Performancexe2x80x9d, Critical Reviews of Food Science and Nutrition, 35(1and2):131-145 (1995).
A good example of physical and mental stress can be found in the military training exercises utilized by modern armies around the world. The military trainees experience increased incidence of infectious diseases as do populations of humans that are stressed by natural disasters, wartime refugee status and the like. A paper by Bernton, et al., xe2x80x9cAdaptation to Chronic Stress in Military Trainees, Ann NY Acad. Sci., Vol. 774 (217-231), 1995, reports the findings of studies investigating metabolic, cognitive, endocrinologic and immunologic adaptation in soldiers enrolled at the U.S. Army Ranger School during eight (8) weeks of extremely stressful training. The stress was both physical and emotional.
During the field training, the soldiers were provided only field rations. The ration provided fewer calories than those expended during the field exercise. As the ration provided fewer calories than those expended during the exercise, the soldier was in constant hunger and a progressive weight loss occurred during the exercise. Immune system suppression was evaluated by delayed type hypersensitivity by epicutaneous skin testing to seven (7) antigens. Significant suppression in both the mean number of positive skin tests and total millimeters of skin test induration was noted. Furthermore, it has been found in hospitalized patients that anergy as assessed by delayed type skin hypersensitivity indicates an increased risk of infection and mortality. See Christou N V, et al., xe2x80x9cTwo techniques of measurement of the delayed hypersensitivity skin test response for the assessment of bacterial host resistance.xe2x80x9d World J. Surg., 1985;5:798-806 and Christou N V, et al., xe2x80x9cThe delayed hypersensitivity response and host resistance in surgical patients 20 years later.xe2x80x9d Ann Surg. 1995;222:534-461. These papers make no suggestion of a nutritional product that would successfully protect a stressed immune system from degradation.
U.S. Pat. No. 4,981,844 to Alexander, et al., discloses a method of improving the immune response in patients comprising the ingestion of a diet that provides 20-60 kilo calories per kg of patient body weight and wherein 20-80% of the calories are derived from linoleic acid. The Alexander, et al., patent also teaches the consumption of from 100-1000 IU per day of vitamin E.
U.S. Pat. No. 5,556,644 to Chandra discloses a multi-nutrient nutritional supplement designed-to be effective in increasing immunity and decreasing the instances and severity of infection among the elderly. This patent specifically teaches the consumption of a nutritional supplement having recited levels of various vitamins and minerals. The patent more specifically teaches the consumption of the nutritional supplement by the elderly to improve their immunological status.
U.S. Pat. No. 5,444,054 to Garleb, et al., discloses a nutritional product for patients suffering from ulcerative colitis or inflammation of the colon. The nutritional product utilizes an oil blend containing specified fatty acids and a source of indigestible carbohydrate. The indigestible carbohydrate is disclosed as being metabolized to short-chain fatty acids by microorganisms present in the human colon.
U.S. Pat. No. 5,223,285 to DeMichele, et al., discloses a liquid nutritional product that contains a specific lipid blend for pulmonary patients. This patent discloses that the lipid should have a particular ratio of n-6 to n-3 fatty acids. Further, this reference describes a nutritional product containing quantities of nutrients having antioxidative properties in vivo. Examples of such antioxidative nutrients include xcex2-Carotene, vitamin E, vitamin C, selenium and taurine.
U.S. Pat. No. 4,871,768 to Bistrian, et al., describes a dietary supplement that contains a structured glyceride comprising n-3 fatty acids and medium chain fatty acids. This patent describes synthetic triglycerides or structured lipids that provide a high energy fat source and fatty acids that assist in fighting infection. This patent also describes a method of minimizing the effects of infection and minimizing the effects of subsequent infection by administering a diet containing 10-80% by weight of an oily fraction comprising glycerol, fatty acids and combinations thereof wherein 50-90% of the fatty acids are caprylic acid, capric acid or mixtures thereof and 10-50% by weight of n-3 fatty acids. This reference teaches that the dietary supplement will not prevent the onset of infections, however, it will promote survival of infected patients. This patent fails to suggest that stress induced down regulation of the immune system can be lessened by a nutritional composition that comprises (1) a structured glyceride; and (2) an antioxidant system comprising at least vitamin E, vitamin C, selenium and xcex2-Carotene.
WO 96/31457 (PCT GB 96/00828) to Horrobin, et al., describes structured lipids with two (2) or three (3) different fatty acids chosen from the twelve (12) essential fatty acids, oleic acid and other fatty acids containing 8-26 carbon atoms. The Horrobin structured lipids are suggested as pharmaceuticals for the treatment or prevention of disease in that abnormalities of the essential fatty acid metabolism have been identified.
U.S. Pat. No. 4,607,052 to Mendy, et al., describes triglycerides wherein specific polyunsaturated acyl fragments are present at the sn-2 position of the glycerol molecule. The structured lipids of Mendy, et al., are described as being useful for the treatment of lipid digestion problems, metabolic diseases, nutritional deficiencies, hypertension and in conditions where immune modulation is desired. There is no teaching nor suggestion in the Mendy, et al., patent that a structured glyceride, when combined with a specific antioxidant system, would be effective in reducing the immunosuppression typically seen in an animal subjected to stress.
WO 96/39869 to Schmitz, et al., discloses a health food product having various ingredients in discrete portions of a solid food product. One portion is taught to contain antioxidants while the second portion contains fat, protein, and carbohydrate.
The prior art fails to suggest or disclose a nutritional composition comprising a structured glyceride component and a unique antioxidant system that is effective in reducing or minimizing stressed induced immune system dysregulation or suppression. The inventive nutritional composition will sometimes hereinafter be referred to as an immunonutritional. The prior art also fails to suggest or disclose a method to reduce or prevent stress induced suppression of the immune system wherein the method comprises administration of a nutritional-product comprising a structured glyceride component and an antioxidant system to a individual.